PT  - JOURNAL ARTICLE
AU  - Biot, Claire
AU  - Rentsch, Cyrill A.
AU  - Gsponer, Joel R.
AU  - Birkhäuser, Frédéric D.
AU  - Jusforgues-Saklani, Hélène
AU  - Lemaître, Fabrice
AU  - Auriau, Charlotte
AU  - Bachmann, Alexander
AU  - Bousso, Philippe
AU  - Demangel, Caroline
AU  - Peduto, Lucie
AU  - Thalmann, George N.
AU  - Albert, Matthew L.
TI  - Preexisting BCG-Specific T Cells Improve Intravesical Immunotherapy for Bladder Cancer
AID  - 10.1126/scitranslmed.3003586
DP  - 2012 Jun 06
TA  - Science Translational Medicine
PG  - 137ra72--137ra72
VI  - 4
IP  - 137
4099  - http://stm.sciencemag.org/content/4/137/137ra72.short
4100  - http://stm.sciencemag.org/content/4/137/137ra72.full
AB  - Therapeutic intravesical instillation of bacillus Calmette-Guérin (BCG) is effective at triggering inflammation and eliciting successful tumor immunity in patients with non–muscle invasive bladder cancer, with 50 to 70% clinical response. Therapeutic success relies on repeated instillations of live BCG administered as adjuvant therapy shortly after tumor resection; however, the precise mechanisms remain unclear. Using an experimental model, we demonstrate that after a single instillation, BCG could disseminate to bladder draining lymph nodes and prime interferon-γ–producing T cells. Nonetheless, repeated instillations with live BCG were necessary for a robust T cell infiltration into the bladder. Parenteral exposure to BCG before instillation overcame this requirement; after the first intravesical instillation, BCG triggered a more robust acute inflammatory process and accelerated T cell entry into the bladder, as compared to the standard protocol. Moreover, parenteral exposure to BCG before intravesical treatment of an orthotopic tumor markedly improved response to therapy. Indeed, patients with sustained preexisting immunity to BCG showed a significant improvement in recurrence-free survival. Together, these data suggest that monitoring patients’ response to purified protein derivative, and, in their absence, boosting BCG responses by parenteral exposure before intravesical treatment initiation, may be a safe and effective means of improving intravesical BCG-induced clinical responses.